Effect of KRAS codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group

BMC Cancer

Research Article

Richard Greil¹  Ulrich Graeven²  Dominik P Modest³  Nina Bruns⁴  Karsten Schulmann⁴  Anke Reinacher-Schick⁵  Wolff Schmiegel⁶  Dirk Arnold⁷  Andrea Tannapfel⁸  Malgorzata Jaworska⁸  Rainer Porschen⁹ 

[1] 3rd Medical Department with Hematology and Medical Oncology, Oncologic Centre Paracelsus Medical University, Salzburg, Austria;Department of Hematology, Oncology and Gastroenterology, Kliniken Maria Hilf, Mönchengladbach, Germany;Department of Internal Medicine III, Klinikum der Universität, München, Germany;Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany;Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany;Center for Clinical Studies in Oncology within PURE, Ruhr-University Bochum, Bochum, Germany;Medical Department, Knappschaftskrankenhaus, Ruhr-University Bochum, In der Schornau 23-25, 44892, Bochum, Germany;Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany;Department of Gastroenterology & Hepatology, Berufsgenossenschaftliches Klinikum Bergmannsheil, Ruhr-University Bochum, Bochum, Germany;Center for Clinical Studies in Oncology within PURE, Ruhr-University Bochum, Bochum, Germany;Hubertus Wald Cancer Center, University Hospital Hamburg, Hamburg, Germany;Institute of Pathology, Ruhr-University Bochum, Bochum, Germany;Klinikum Bremen-Ost, Bremen, Germany;

关键词: Codon 13 mutation;    Colorectal cancer;    KRAS;    Oxaliplatin;    Prognosis;   

DOI  :  10.1186/1471-2407-12-349

 received in 2011-09-18, accepted in 2012-06-26,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTo evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.MethodsTumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).Results201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.ConclusionsOur data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.Trial registration number2002-04-017

【 授权许可】

CC BY   
© Reinacher-Schick et al.; licensee BioMed Central Ltd. 2012